原发性胆汁性肝硬化患者外周血淋巴细胞亚群和细胞因子水平及药物对其的影响

目的 研究原发性胆汁性肝硬化(PBC)患者外周血淋巴细胞亚群、细胞因子特点及药物对其的影响.方法 82例初诊PBC患者随机分为熊去氧胆酸组(28例)、熊去氧胆酸联合泼尼松龙组(27例)、熊去氧胆酸联合硫唑嘌呤组(27例),检测治疗前和治疗3、6个月时外周血淋巴细胞亚群和细胞因子水平.另设健康对照组20例.结果 与健康对照组相比,PBC患者外周血CD_4~+T细胞比例升高42.10±0.97)%比(36.40±2.18)%],IFN7(36.40±1.49)ng/L比(25.70±2.50)ns/L]、IL-2(68.30±3.14)ng/L比(37.10±3.72)ns/L]、IL-4(53.30±2.49)ns/L比(40.70±3.78)ns/L]、IL-6(41.30±2.91)ng/L比(31.20±3.14)ng/L]、TNFα(30.10±0.94)ng/L比(23.50±1.68)ng/L]、IL一1β(55.80±2.38)ng/L比(42.40±3.03)ns/L]、转化生长因子β(TGFβ)(68.10±2.63)ng/L比(59.10±2.29)ng/L]水平升高;外周血TNFα水平与AIJT、AST、总胆红素(TBil)、直接胆红素(DBil)、Mayo危险评分呈正相关(r分别为0.355、0.390、0.409、0.397、0.293,P<0.05).治疗后,熊去氧胆酸组外周血CD~+_4T细胞比例下降;熊去氧胆酸组IFNγ、IL-4、IL-6水平在治疗3个月后降低,而6个月后升高;熊去氧胆酸联合泼尼松龙组、熊去氧胆酸联合硫唑嘌呤组IFNγ、IL-4、IL-6均较治疗前降低.3组PBC患者治疗后IL-2、TNFα均较治疗前降低.结论 PBC患者外周血同时存在Th1型和Th2型细胞因子异常,且以Th1型细胞因子异常为主,提示PBC是以细胞免疫为主的自身免疫病.IFNγ、TNFα与病情相关.三种治疗方案对免疫系统的调节不完全相同.

The characteristics of peripheral lymphocytic subsets and cytokines in primary biliary and their changes to drug treatment

Objective To investigate the characteristics of peripheral lymphocytic subsets and cytokines in patients with primary biliary cirrhosis( PBC) and their changes after therapy. Methods Eighty two patients with untreated PBC were divided randomly into three groups. Group U (28 patients) were treated with ursodeoxycholic acid ( UDCA) , group UP (27 patients) were treated with UDCA and prednisonlone, while group UA (27 patients) were treated with UDCA and azatharaprine. Levels of peripheral lymphocytic subsets and cytokines were monitored at 0, 3, 6 months after therapy. Twenty healthy people were included as healthy control ( HC). Results Compared with HC, the percentage of CD/ T cell (P = 0. 044) increased in PBC; the levels of IFNγ(P = 0. 001), IL-2 (P =0. 000) , IL-4 (P =0. 010) , IL-6 (P = 0. 029) , tumor necrosis factora ( TNFα ) ( P = 0. 000) , IL-1β ( P = 0. 008 ) and transforming growth factorβ(TGFβ) (P =0. 069) increased in PBC. The level of TNFa in peripheral was correlated with those of ALT (P=0.005), AST (P=0.002), total bilirubin(Tbil) (P=0.001), direct bilirubin( Dbil) (P=0. 002) , and mayo risk score(MRS) (P=0. 020). The percentage of CD_4~+T cell decreased in group U. In group U, the levels of IFNγ,IL-4,IL-6 all decreased after therapy at the third month, but rebounded thereafter. In group of UP and UA, the levels of IFN-γ, IL-4, IL-6 were suppressed below the levels of baseline after therapy.Levels of TNFa and IL-2 decreased in all three groups after therapy. Conclusions Levels of both Thl and Th2 related cytokines are abnormal in the peripheral blood of patients with PBC. The abnormal levels of Thl related cytokine indicated that PBC is a cell immunity based autoimmune disease. IFNγ,TNFα are directly related to the disease. The three treatments have different effects on the adjustment of the immune system.